title: The chemokine CCL3 promotes experimental liver fibrosis in mice.
abstract: Liver fibrosis is associated with infiltrating immune cells and activation of hepatic stellate cells. We here aimed to investigate the effects of the CC chemokine CCL3, also known as macrophage inflammatory protein-1α, in two different fibrosis models. To this end, we treated mice either with carbon tetrachloride or with a methionine- and choline-deficient diet to induce fibrosis in CCL3 deficient and wild-type mice. The results show that the protein expression of CCL3 is increased in wild-type mice after chronic liver injury. Deletion of CCL3 exhibited reduced liver fibrosis compared to their wild-type counterparts. We could validate these results by treating the two mouse groups with either carbon tetrachloride or by feeding a methionine- and choline-deficient diet. In these models, lack of CCL3 is functionally associated with reduced stellate cell activation and liver immune cell infiltration. In vitro, we show that CCL3 leads to increased proliferation and migration of hepatic stellate cells. In conclusion, our results define the chemokine CCL3 as a mediator of experimental liver fibrosis. Thus, therapeutic modulation of CCL3 might be a promising target for chronic liver diseases.
authors.affiliation: Medical Department III, University Hospital Aachen, Aachen, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Heinrichs
authors.forename: Marie-Luise
authors.initials: ML
authors.lastname: Berres
authors.forename: Andreas
authors.initials: A
authors.lastname: Nellen
authors.forename: Petra
authors.initials: P
authors.lastname: Fischer
authors.forename: David
authors.initials: D
authors.lastname: Scholten
authors.forename: Christian
authors.initials: C
authors.lastname: Trautwein
authors.forename: Hermann E
authors.initials: HE
authors.lastname: Wasmuth
authors.forename: Hacer
authors.initials: H
authors.lastname: Sahin
mesh_terms: D000818:Animals; D002251:Carbon Tetrachloride / Q000008:administration & dosage; D049109:Cell Proliferation; D054405:Chemokine CCL3 / Q000502:physiology*; D004797:Enzyme-Linked Immunosorbent Assay; D050155:Lipogenesis; D008103:Liver Cirrhosis / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D013601:T-Lymphocytes / Q000166:cytology
chemical_list: C496534:Ccl3 protein, mouse; D054405:Chemokine CCL3; D002251:Carbon Tetrachloride